Liver function tests

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  1. 1. Moderator Dr. Saroj Jaswal Submitted by 51-60
  2. 2. GROSS ANATOMY Two lobes (falciform ligament) Blood supply : Hepatic artery(oxygen)& Portal vein(nutrients) veinous supply : hepatic veins , inferior vena ceva microscopic units lobules functional units of liver Each lobule is a hexagonal centrally located vein with portal triads
  3. 3. BIOCHEMICAL FUNCTIONS The liver performs four major functions : Excretion / secretion Metabolism Detoxification Storage 1. Synthetic functions : Plasma proteins albumin(osmotic pressure) , carrier proteins ( transport of elements Fe Cu) , globulins , coagulation factors. Cholestrol precursor of steroid hormones , bile acids and 7-dehydrocholestrol. Bile acids- to absorb lipid nutrients from the gut , includes fatty acids and fat soluble vitamins .
  4. 4. METABOLISM Carbohydrate metabolism : Liver is an important homeostatic regulator of blood glucose . It can either produce glucose or store glucose . By the following processes : 1. Glycogenesis by converting glucose into glycogen for storage . 2. Glycogenolysis ATP is required , glycogen is again converted back into glucose . 3. Gluconeogenesis formation of glucose from non precursor carbohydrates such as lactate , glucogenic amino acid and propinyl CoA .
  5. 5. AMINO-ACID METABOLISM PROTEINS get breakdown in the intestine into amino acids and reach liver by portal vein ; utilized to form different proteins like globulin , albumin , coagulation factors .. LIPID METABOLISM : Fatty acids catabolised to release CoA used for TCA cycle and ETC to release energy . Acetyl CoA converted to ketone bodies acetone , acetoacetate and hydroxybutyric acid . Liver synthesis apoprotein part of lipoproteins transportation of lipids into circulation .
  6. 6. PROTECTIVE FUNCTION & DETOXIFICATION Exogenous substances : It detoxify toxic substances hydrolysis , hydroxylation ,oxidation , reduction and demethylation . More soluble in water and easily excreted through urine . Drugs metabolised by P450 enzyme system of liver , convert drugs into more soluble form which in due course conjugate with sub. Like glycine , glucouronic acid to get excreted in urine . Endogenous substances Kupffer cells perform phagocytosis to eliminate foreign cmpds . For eg. NH3 is detoxified urea and metabolism of xenobiotics ( detoxification )
  7. 7. WHAT IS PURPOSE OF LFTS? LFTs alone do not give the physician full information, but used in combination with a careful history, physical examination (particularly ultrasound and CT Scanning), can contribute to making an accurate diagnosis of the specific liver disorder. Different tests will show abnormalities in response to liver inflammation liver injury due to drugs, alcohol, toxins, viruses Liver malfunction due to blockage of the flow of bile Liver cancers
  8. 8. CLASSIFICATION OF LFTS Synthetic function of liver- a. Serum proteins albumin,globulin,ceruloplasmin haptoglobin , alpha fetoprotein , alpha 1 antitrypsin levels b. Prothrombin time Serum Enzymes(liver enzyme panel) a. Indicating hepatocellular damage- ALT , AST b. Indicating obstruction- ALP, GGT Based on detoxification function a. Blood ammonia b. Hippuric acid test Hepatic excretory function- a. serum- bilirubin levels, conjugated and unconjugated b. Urine bile pigments , bile salts and urobilinogen
  9. 9. 1)SERUM ALBUMIN LEVEL Normal Value- 3.5 to 5 g/dl Albumin is major protein- responsible for OSMOTIC pressure in vascular system Half life: 20 days, low level in all chronic diseases of liver Normal A/G ratio is 1.2 to 1.5 :1 Reverses in case of cirrhosis due to hypoalbuminemia and hypergammaglobulinemia.
  10. 10. 2) SERUM GLOBULIN Alpha and beta globulins synthesized by liver and immunoglobulin by lymphocytes Normal value - 2.5 to 3.5 g/dl Cirrhotic liver cannot clear bacteria, antibodies against intestinal bacteria seen. Ig A Inc. in alcoholic liver disease Ig M - Primary biliary cirrhosis.. Ig G - Auto immune hepatitis.
  11. 11. 3) PROTHROMBIN TIME Prothrombin is synthesized by liver Half life 6 hrs so it indicate present function of liver PT :blood test, time taken by blood to clot Normal value : 10 to 15 sec. PT is Prolonged - liver losses 80% of reserve capacity Commonly PT is used for detecting liver coagulopathies Note : Vit K deficiency Prolongs PT time But In case of LIVER diseases : PT remains prolonged even after parenteral administration of Vit. K
  12. 12. 4) 1-ANTITRYPSIN (AAT) Most abundant 1-globulin and acute phase reactant Inactivates : serum proteases Normal values : 90 to 200 mg/dl It has multiple alleles , individuals possessing PiZZ allele : deficient activity of this enzyme : Liver cirrhosis Low levels Neonatal cholestasis, emphysema High levels acute trauma, infection
  13. 13. 5) HAPTOGLOBIN Another major 2 protein synthesised in liver. Normal values: 30- 200 mg/dl Function transports free Hb in the plasma to reticuloendothelial system (RES) Low levels lead to ppt of free Hb in kidneys and cause damage Turnover rates are less than albumin used to Identify recent changes in the liver. Low levels Severe hepatocellular diseases (deficient synthesis), hemolytic disease(rapid degradation) High levels Inflammatory processes , myocardial infarction
  14. 14. 6) -FETOPROTEIN Normal component of fetal blood., disappears after few weeks of birth. Normal range-up to 1 year of age < 30ng/ml adults(M and non pregnant F) < 15ng/ml Tumor marker Maternal serum AFP level Inc. in fetal open tube neural defect and dec. in foetal down syndrome Mild Inc. Chronic hepatitis or cirrhosis Drastic Inc. hepatocellular carcinoma, germ cell tumour and teratoma of ovary
  15. 15. 7) CERULOPLASMIN Synthesized by Hepatic parenchymal cells and small part by lymphocytes Transport : Cu Normal levels: males 22- 40mg/dl females 25-60mg/dl pregnancy 30-120 mg/dl Low levels Wilson's hepatolenticular degeneration High levels Acute Hepatitis, hemochromatosis, obstructive biliary disease
  16. 16. 8)TRANSTHYREITN (PRE-ALBUMIN) Produced by liver Transport thyroxine and triidothyronine Half life 2 days , hence useful parameter to assess hepatic function early in course of liver disorders.
  17. 17. TEST BASED ON SERUM ENZYMES A. Enzymes indicating Hepatocellular Damage Alanine amino transferase (ALT) Serum Glutamate Pyruvate transaminase (SGPT) Source - liver, cardiac muscle , skeletal muscle. Increased when cells of the liver have been inflamed or necrosed. Normal serum level : male- 13-35 U/L female 10-35 U/L SGPT PLP
  18. 18. Abnormal levels Only ALT are elevated in:- 1. AMI rise within 6-8 hrs and remain upto 5 days 2. Pulmonary embolism Aspartate amino transferases (AST) Serum glutamate oxaloacetate transaminase (SGOT) Source- more liver specific Moderate 50 - 100 Chronic liver diseases,hepatitis C, NASH(non alcoholic steatohepatitis ) Very high 300-1000 Acute hepatitis , toxic or viral in origin AST PLP
  19. 19. Normal level : 8-20 U/L Normal AST: ALT ratio 0.8 ratio > 2 AST is higher Alcoholic hepatitis, hepatitis with cirrhosis , NASH , erythromycin treatment Ratio < 0.8 ALT is higher Acute hepatocellular injury, toxic exposure ,extra hepatic obstruction elevated liver diseases, myocardial infarct, muscle disease
  20. 20. B. Markers of obstructive liver disease Alkaline Phosphatase (ALP) Source: liver, bone, placenta and intestine. ALP is a hydrolase enzyme responsible for removing phosphate groups from many types of molecules, including nucleotides and proteins. phosphomonoester ALP alcohol + phoshate ion Normal level: 40-125 U/L Levels are significantly higher in children and pregnant women. Moderate increase 2-3 times Hepatic diseases includes infective hepatitis,hepatocellular carcinoma Very high levels 10-12 times Obstructive jaundice (gall stones) Drastically high levels More than 12 times Not related to liver disease but Bones disease such as rickets, osteomalacia
  21. 21. ISOENZYMES OF ALP Iso enzyme location Increased in Alpha 1 ALP Epithelial cells of biliary canaliculi Obstructive jaundice Alpha 2 heat labile ALP Hepatic cells Alpha 2 heat stable ALP Placental origin (regan iso enzyme) Pregnancy and inhibited by phenylalanine Pre beta ALP Bone origin Pagets disease, rickets osteomalacia Gamma ALP Intestinal cells Ulcerative colitis 5- Nucleotidase Normal range 2-17 U/L Function ; hydrolysis of nucleoside 5 phosphate esters Clinical significance Sensitive and specific for hepatobiliary disorders (HBD), obstructive biliary diseases Normal pregnancy, bone growth and bone diseases do not affect 5' NT In pts with HBD, changes in ALP are usually followed by similar changes in 5' NT
  22. 22. GAMMA GLUTAMYL TRANSFERASE (GGT) 1. Function Glutathione + amino acid GGT glutamyl peptide + cysteinylglycine regulate glutathione levels 2.Source - liver, kidney, pancreas, intestinal cells absent in bone 3.Normal serum levels : 10-30 U/L 4. Diagnostic signicficance hepatic microsomal enzyme GGT elevation differentiate ALP increase levels ,seen in biliary tract diseases In alcoholic liver disease GGT levels may be parallel to alcohol intake , even when other LFTs are in Normal range. diseases pancreatic disease , MI ,pulmonary disease Drugs warfarin , antidepressants
  23. 23. TEST BASED ON DETOXIFICATIOM Blood ammonia level Normal level: 10-50 mcg/dl Index of urea synthesis by liver, marker of hepatic encaphlopathy Ammonia is converted to urea by liver Increased levels 1. cirrhosis 2. portocaval anastomoses Hippuric acid test Benzoyl glycine Reaction benzoic acid+glycine = hippuric acid Ingestion of sodium benzoate thn hourly excretion hippuric acid is constant Decreases when the liver fails to detoxify
  24. 24. Oral Glucose tolerance test Gluco